Four years ago, Professor Kaptchuk, OMD, received a Midcareer K24 award. This is a renewal application. The principal investigator's short-term goal is to obtain protected time to 1) stabilize and expand his training of the next generation of CAM scientists and 2) develop a multi-disciplinary research program in placebo, East Asian medicine and complementary and alternative medicine (CAM). His long-term goal, for his work and that of his trainees, is to make clinically relevant contributions to clinical care. Ted Kaptchk is Associate Professor of Medicine at Harvard Medical School. His research and scholarship integrates concepts, research designs and analytic methods drawn from the basic, clinical, and social sciences, as well as the humanities. Achievements in first four years of K24: The principal investigator has completed three major RCTs investigating placebo effects and two RCTs testing acupuncture's efficacy. He also performed groundbreaking studies identifying the brain circuitry of responses to placebo and acupuncture. In this period, the principal investigator published 70 articles, eight as first author and 28 as senior author. The principal investigator also received two new R01s concerned with both placebo/expectation effects and acupuncture and, as senior co-investigator, a P01, U19 and various R21s. During the initial K24 period, he has been primary or co-primary CAM mentor for 25 trainees with doctoral degrees. Eleven trainees held K training awards. His trainees authored 53 first-authored peer-reviewed publications and had 82 co-authorships. He expects to expand these successful efforts in a renewal period. Harvard University and its 17 teaching hospitals comprise an NIH affiliated CTSA institutional consortium. Professor Kaptchuk is fully integrated into the CTSA and has recently been appointed director of Harvard-wide Program in Placebo Studies and Therapeutic Encounter. He is active in many Harvard fellowship programs including serving as associate director of the Harvard-wide NCCAM-funded T32 CAM fellowship program. The principal investigator will take relevant courses in bioethics, philosophy of science, immunology, and statistics and engage in hands-on training in molecular and neuroimaging research. In the first four years of his K24, the principal investigator developed a research portfolio that includes translational research in irritable bowel syndrome, asthma, depression, osteoarthritis, and migraine. These research areas will be expanded. He is currently using fMRI to extend his previous work on the neural circuitry of placebo and acupuncture in healthy volunteers to patients with chronic pain disorders. A PET-fMRI study will investigate placebo responses dependent on morphine conditioning verses ketorolac conditioning. He will initiate fMRI experiments to elucidate the neurobiology of the physician component of the patient-physician relationship. The principal investigator is also investigating specific biological pathways implicated in placebo and acupuncture responses and their mechanisms of regulation by concurrently examining circulating serum cytokines, auto antibodies, microRNAs and polymorphisms (SNPs) in genes of interest.